Cytotoxicity and genotoxicity of hexavalent chromium in human and North Atlantic right whale (Eubalaena glacialis) lung cells

Abstract

Humans and cetaceans are exposed to a wide range of contaminants. In this study, we compared the cytotoxic and genotoxic effects of a metal pollutant, hexavalent chromium [Cr(VI)], which has been shown to cause damage in lung cells from both humans and North Atlantic right whales. Our results show that Cr induces increased cell death and chromosome damage in lung cells from both species with increasing intracellular Cr ion levels. Soluble Cr(VI) induced less of a cytotoxic and genotoxic effect based on administered dose in right whale (Eubalaena glacialis) cells than in human (Homo sapiens) cells. Whereas, particulate Cr(VI) induced a similar cytotoxic effect but less of a genotoxic effect based on administered dose in right whale cells than in human cells. Differences in chromium ion uptake explained soluble chromate-induced cell death but not all of the soluble chromate-induced chromosome damage. Uptake differences of lead ions could explain the differences in particulate chromate-induced toxicity. The data show that both forms of Cr(VI) are less genotoxic to right whale than human lung cells, and that soluble Cr(VI) induces a similar cytotoxic effect in both right whale and human cells, while particulate Cr(VI) is more cytotoxic to right whale lung cells.

Figure 1. Human Lung Cells Take Up Greater Amounts of Cr(VI) than North Atlantic Right Whale Lung Cells

This figure shows that exposure to Cr(VI) induces Cr ion uptake in both human and North Atlantic right whale lung cells in a concentration-dependent manner. Data represent the average of 3 independent experiments. Error bars = standard error of the mean. (A) Cr uptake after sodium chromate treatment. (B) Cr uptake after lead chromate treatment.

Figure 1. Human Lung Cells Take Up Greater Amounts of Cr(VI) than North Atlantic Right Whale Lung Cells

This figure shows that exposure to Cr(VI) induces Cr ion uptake in both human and North Atlantic right whale lung cells in a concentration-dependent manner. Data represent the average of 3 independent experiments. Error bars = standard error of the mean. (A) Cr uptake after sodium chromate treatment. (B) Cr uptake after lead chromate treatment.

Figure 2. Reduced Cr(VI)-Induced Cytotoxicity in North Atlantic Right Whale Lung Cells Relative to Human Lung Cells Is Due to Differences in Cr Ion Uptake for Soluble Cr(VI), But Not for Particulate Cr(VI)

This figure shows that exposure to Cr(VI) induces cytotoxicity in human and North Atlantic right whale lung cells in a concentration-dependent manner, based on administered dose (p<0.01). Data represent the average of 3 independent experiments. Error bars = standard error of the mean. (A) Sodium chromate cytotoxicity based on administered dose. (B) Lead chromate cytotoxicity based on administered dose. (C) Cytotoxicity for sodium chromate based on intracellular Cr ion level. (D) Cytotoxicity for lead chromate based on intracellular Cr ion level. (E) Cytotoxicity for both sodium and lead chromate based on intracellular Cr ion level for right whale lung cells.

Figure 2. Reduced Cr(VI)-Induced Cytotoxicity in North Atlantic Right Whale Lung Cells Relative to Human Lung Cells Is Due to Differences in Cr Ion Uptake for Soluble Cr(VI), But Not for Particulate Cr(VI)

This figure shows that exposure to Cr(VI) induces cytotoxicity in human and North Atlantic right whale lung cells in a concentration-dependent manner, based on administered dose (p<0.01). Data represent the average of 3 independent experiments. Error bars = standard error of the mean. (A) Sodium chromate cytotoxicity based on administered dose. (B) Lead chromate cytotoxicity based on administered dose. (C) Cytotoxicity for sodium chromate based on intracellular Cr ion level. (D) Cytotoxicity for lead chromate based on intracellular Cr ion level. (E) Cytotoxicity for both sodium and lead chromate based on intracellular Cr ion level for right whale lung cells.

Figure 2. Reduced Cr(VI)-Induced Cytotoxicity in North Atlantic Right Whale Lung Cells Relative to Human Lung Cells Is Due to Differences in Cr Ion Uptake for Soluble Cr(VI), But Not for Particulate Cr(VI)

This figure shows that exposure to Cr(VI) induces cytotoxicity in human and North Atlantic right whale lung cells in a concentration-dependent manner, based on administered dose (p<0.01). Data represent the average of 3 independent experiments. Error bars = standard error of the mean. (A) Sodium chromate cytotoxicity based on administered dose. (B) Lead chromate cytotoxicity based on administered dose. (C) Cytotoxicity for sodium chromate based on intracellular Cr ion level. (D) Cytotoxicity for lead chromate based on intracellular Cr ion level. (E) Cytotoxicity for both sodium and lead chromate based on intracellular Cr ion level for right whale lung cells.

Figure 2. Reduced Cr(VI)-Induced Cytotoxicity in North Atlantic Right Whale Lung Cells Relative to Human Lung Cells Is Due to Differences in Cr Ion Uptake for Soluble Cr(VI), But Not for Particulate Cr(VI)

This figure shows that exposure to Cr(VI) induces cytotoxicity in human and North Atlantic right whale lung cells in a concentration-dependent manner, based on administered dose (p<0.01). Data represent the average of 3 independent experiments. Error bars = standard error of the mean. (A) Sodium chromate cytotoxicity based on administered dose. (B) Lead chromate cytotoxicity based on administered dose. (C) Cytotoxicity for sodium chromate based on intracellular Cr ion level. (D) Cytotoxicity for lead chromate based on intracellular Cr ion level. (E) Cytotoxicity for both sodium and lead chromate based on intracellular Cr ion level for right whale lung cells.

Figure 3. Reduced Soluble Cr(VI)-Induced Genotoxicity in North Atlantic Right Whale Lung Cells Relative to Human Lung Cells Is Not Due to Differences in Cr Ion Uptake

This figure shows that exposure to sodium chromate induces genotoxicity in both human and right whale lung cells in a concentration-dependent manner. (A) Sodium chromate-induced metaphases with chromosome damage based on administered dose. (B) Sodium chromate-induced total chromosome damage in 100 metaphases based on administered dose. (C) Percent metaphases with damage based on intracellular Cr ion level. (D) Total chromosome damage in 100 metaphases based on intracellular Cr ion level. Data represent the average of 3 independent experiments. Error bars = standard error of the mean. NM – no metaphases observed.

Figure 3. Reduced Soluble Cr(VI)-Induced Genotoxicity in North Atlantic Right Whale Lung Cells Relative to Human Lung Cells Is Not Due to Differences in Cr Ion Uptake

This figure shows that exposure to sodium chromate induces genotoxicity in both human and right whale lung cells in a concentration-dependent manner. (A) Sodium chromate-induced metaphases with chromosome damage based on administered dose. (B) Sodium chromate-induced total chromosome damage in 100 metaphases based on administered dose. (C) Percent metaphases with damage based on intracellular Cr ion level. (D) Total chromosome damage in 100 metaphases based on intracellular Cr ion level. Data represent the average of 3 independent experiments. Error bars = standard error of the mean. NM – no metaphases observed.

Figure 4. Reduced Particulate Cr(VI)-Induced Genotoxicity in North Atlantic Right Whale Lung Cells Relative to Human Lung Cells May Be Due to Differences in Cr Ion Uptake

This figure shows that exposure to lead chromate induces genotoxicity in both human and right whale lung cells in a concentration-dependent manner. (A) Lead chromate-induced metaphases with chromosome damage based on administered dose. (B) Lead chromate-induced total chromosome damage in 100 metaphases based on administered dose. (C) Percent metaphases with damage for based on intracellular Cr ion level. (D) Total chromosome damage in 100 metaphases based on intracellular Cr ion level. Data represent the average of 3 independent experiments. Error bars = standard error of the mean. NM – no metaphases observed.

Figure 4. Reduced Particulate Cr(VI)-Induced Genotoxicity in North Atlantic Right Whale Lung Cells Relative to Human Lung Cells May Be Due to Differences in Cr Ion Uptake

This figure shows that exposure to lead chromate induces genotoxicity in both human and right whale lung cells in a concentration-dependent manner. (A) Lead chromate-induced metaphases with chromosome damage based on administered dose. (B) Lead chromate-induced total chromosome damage in 100 metaphases based on administered dose. (C) Percent metaphases with damage for based on intracellular Cr ion level. (D) Total chromosome damage in 100 metaphases based on intracellular Cr ion level. Data represent the average of 3 independent experiments. Error bars = standard error of the mean. NM – no metaphases observed.

Figure 5. Particulate and Soluble Cr(VI) Induce Similar Amounts of Genotoxicity Based on Intracellular Cr Ion Levels

This figure shows that exposure to both soluble and particulate Cr(VI) induces genotoxicity with increasing intracellular Cr ion levels in right whale lung cells in a similar manner. (A) Soluble and particulate Cr(VI) induces similar amount of metaphase with chromosome damage in right whale lung cells. (B) Soluble and particulate Cr(VI) induces similar amount of total chromosome damage in 100 metaphases in both human and right whale lung cells. Data represent the average of 3 independent experiments. Error bars = standard error of the mean. ND – not done; NM – no metaphases.